Monoclonal antibodies are a more recent approach to antiviral immunotherapy. These antibodies have been developed for viruses such as HIV, although extensive evaluation has yet to be undertaken. A speciﬁc monoclonal antibody against cellu- lar IL-2 receptors (daclizumab) has been developed and eval- uated for the prevention of graft rejection in renal transplant recipients (356). In these graft recipients, daclizumab led to a decreased incidence of CMV infection when added to conven- tional dual immunosuppressive therapy, but had no effect when added to triple therapy. Additional development and studies will be needed.
The only licensed form of monoclonal antibodies avail- able is palivizumab (Synagis) for RSV infection. This is a humanized preparation of monoclonal antibodies directed at the F glycoprotein, a speciﬁc surface protein of RSV (357). Because palivizumab is not produced from human blood prod- ucts, it carries no risk of infectious contamination. Adminis- tration of the preparation is more convenient than RSV-IG, requiring 1 intramuscular injection rather than a 4-hour intravenous infusion of the hyperimmune globulin. In addi- tion, product shortages are not expected since the preparation can easily be produced in large batches.
In a large, placebo-controlled clinical trial of high-risk infants, palivizumab led to a 55% reduction in RSV hospi- talization, a 42% reduction in the number of hospitalization days, and a 57% reduction in intensive-care unit days due to RSV infection (358). Adverse effects are rare and mini- mal. When comparing palivizumab and placebo, there were no signiﬁcant differences in the rates of side effects or the development of antibodies to monoclonal antibody (359), but an increase in aminotransferase levels was noted in the palivizumab group compared with placebo (290). Viral resistance has not yet been detected with the use of palivi- zumab (360).
The implementation of routine immunizations not only has a signiﬁcant impact on the overall incidence of disease, but also markedly decreases the direct and indirect costs associ- ated with health care. For instance, a 1994 study on the cost- effectiveness of a varicella vaccination program in the United States estimated a savings of $384 million per year (361). The cost savings with varicella are mostly due to a decrease in time lost from work by caregivers, although this is signiﬁcant. Vaccines for more serious diseases that often require hospital- ization, such as RSV in infants, will likely result in a more ben- eﬁcial cost-effective proﬁle. The cost savings of the eradication of smallpox, a disease which killed millions of people, approaches the level of inﬁnity when considering the millions more that would have been affected. A similar situation exists for poliomyelitis, which is expected to be eradicated worldwide in the near future. The cost savings for an HIV vaccine would also be phenomenal, when considering the long-term treat- ment and numerous complications that are involved with this chronic infection.
Immunization has successfully led to the reduction in incidence of numerous diseases. Careful development and clinical evaluation have provided safe and effective vaccines with few adverse effects. Many reported adverse reactions fol- lowing vaccination may be coincidental and have no proven direct relationship with the vaccine in question. Although serious side effects may rarely occur from vaccines, a much greater risk for morbidity and mortality results from the fail- ure to become immunized. One vaccine, however, was recently removed from the market due to safety issues. Rotashieldâ was a live, oral tetravalent, rotavirus vaccine that was associ- ated with several cases of intussusception and is considered to be causal (362).
Most associations between vaccines and adverse events are not, however, demonstrated to be causal. For example, the measles mumps rubella (MMR) vaccine was reported recently not to have a causal relationship to autism (363,364). Like- wise, a causal relationship between the hepatitis B vaccine and a variety of autoimmune diseases has been disproven. This vaccine does not increase the risk of multiple sclerosis (365) nor does it cause a relapse of preexisting multiple scle- rosis (366). Nevertheless, suspected relationships between vaccines and adverse events need to be reported to the “Vac- cine Adverse Event Reporting System” (1-800-822-7967) so that the excellent safety record of vaccines can be maintained.
The technology of vaccine development has progressed dramatically in the last decade. While more conventional methods have consisted of whole-killed or live-attenuated viruses, more recent advancements include genetically engi- neered vectors and virus-like particles, among many others. Anticipated vaccine developments in the future show exciting promise in several areas, such as immunization with plants.
Potatoes, tomatoes, and bananas are currently undergoing genetic engineering to express immunizing antigens against infections such as hepatitis B virus and Norwalk virus (367,
368). This form of vaccination would offer a convenient, pain- less, and inexpensive approach to widespread control of dis- ease and would thus be accessible to developing countries.
It is anticipated that the future will bring safe and effec- tive vaccines for a variety of viral diseases, e.g., HIV, hepatitis C, HSV, and HPV. Although no vaccine is available for the therapy of a viral disease, the concept of vaccines is now being expanded by ongoing clinical trials of therapeutic vaccines, e.g., for HIV, HSV, and HPV.